Alfacalcidol
Alfacalcidol is an analogue of vitamin D used for supplementation in humans and as a poultry feed additive.
Alfacalcidol has a weaker impact on calcium metabolism and parathyroid hormone levels than calcitriol; but significant effects on the immune system, including regulatory T cells. It is considered to be a more useful form of vitamin D supplementation, mostly due to its much longer half-life and lower kidney load. It is the most commonly prescribed vitamin D metabolite for patients with end stage renal disease, given that impaired renal function alters the ability to carry out the second hydroxylation step required for the formation of the physiologically active form of vitamin D, 1,25-dihydroxyvitamin D3. Alfacalcidol is an active vitamin D3 metabolite, and therefore does not require the second hydroxylation step in the kidney.
Mechanism of action
Alfacalcidol is a prodrug that is rapidly metabolized in the liver to the active form, calcitriol. As it is already 1α-hydroxylated, it does not require activation in the kidney as cholecalciferol does. After calcitriol binds to its intracellular receptor, the synthesis of a calcium ion-binding protein increases. The compound enhances intestinal absorption of calcium and phosphate, regulates bone mineralization, and promotes calcium reabsorption in the renal tubules.Alfacalcidol prevents deficiency symptoms associated with impaired physiological 1α-hydroxylation of cholecalciferol or calcifediol in the kidneys, particularly in cases of chronic renal insufficiency. Alfacalcidol is not naturally present in the human body and is rapidly converted into calcitriol in the liver.